Hypertension

Physiology, Pathophysiology and Clinical Managements

Jun Tao

Stroke and Ischemic Heart Disease (IHD) Mortality Rate in Each Decade of Age, Versus Usual Systolic BP at the Start of that Decade
Stroke
Age at risk 8089 y 256 128 64 7079 y 6069 y 5059 y 256 128 64 32 16 4049 y 8 4 2 1

IHD
Age at risk 8089 y 7079 y 6069 y 5059 y

Mortality*

32
16 8 4

2
1

0 120

140

160

180

120

140

160

180

Usual SBP (mmHg)

Usual SBP (mmHg)

Reproduced from The Lancet, 360, Lewington et al. pp. 190313 Copyright 2002, with permission from Elsevier

*Floating absolute risk and 95% CI

Introduction

Primary hypertension is a clinical syndrome characterized by the increase in systemic arterial pressure.

95% 0f the patients with hypertension are primary hypertension with unknown causes and 5% secondary hypertension with definitive causes.

Hypertension affects approximately 1 billion individual worldwide. In China the incidence of hypertension is about 180 million individuals.

Primary hypertension

Etiology and pathogenesis

The pathogenesis of primary hypertension is still unclear. There are many factors associate with it.

Genetic factors Sodium intake Renin agiotensin systems Sympathetic nervous system Endothelial dysfunction Insulin resistance Other factors

Genetic factors The offsprings of the hypertensive parents are prone to suffering from essential hypertension compared with that without hypertensive family.

Sodium intake The mechanisms leading to hypertension are due to increased blood volume and the content of the sodium in the smooth muscle cells enhance following subsequent calcium increase.

RAAS system

ReninAngiotensinogen Angiotensin I

Angiothesin II Increase systemic arterial pressure

Sympathetic nervous activation The activation of Sympathetic nervous can augment periphery resistant which increase systemic arterial pressure.

Endothelial dysfunction Endothelium-derived vasodilating factors: NO; PGI2; EDHF. Endothelial-derived vasoconstricting factors:ET; AGII; Superoxide anion.

Insulin resistance Increased absorbability to sodium Increased sympathetic nervous activation Increased cellular contents in sodium and calcium Caused vascular wall hypertrophy

Other factors Obesity Smoking Intake alcohol OSAS Low calcium , magnesium and potassium.

Pathology

Systemic atherosclerosis develops with increased intimal-medium thickness leading to ischemic alterations in target organs such as heart, brain, kidney and peripheral artery.

Blood vessel change

Aorta and large arteries recurrent pulsatile stress produces uncoiling, disruption and calcification of elasstic fibres. At the same time, relatively inelastic collagen is increased.

This is a result of ageing as well as hypertension : both processes therefore cause loss of the normal elastic reservoir funtion of the aorta and large arteries.

This explains one curious feature of elderly hypertensive patients. Diastolic blood pressure in patients with isolated systolic hypertension is inversely related to prognosis.

Medium-sized arteries The predominant pathological change is wall thickening caused by increased deposition of collagenous material.

Resistance vessel The characteristic structural change in smaller arteries and arterioles responsible for peripheral vascular resistance is an increase in wall:lumen ratio.

In recent years it has become clear that what was thought to be a trophic response is largely if not entirely due to rearrangement of smooth muscle cells around a smaller lumen.

Specific organ changes in hypertension

The heart Angina and myocardial infarction in the hypertensive patient are usually due to coronary atheroma.

Left ventricular hypertrophy is demonstrable in about 50 per cent of untreated hypertensive patients when echocardiography is used, and in 5 to 10 per cent with electrocardiography using conventional criteria.

Hpertrophy of left ventricle

Central nervous system Cerebral infarction in a hypertensive patient is usually attributable to atheroma of one of the larger cerebral arteries (usually the middle cerebral artery) and accounts for about 80 percent of the strokes which these patients suffer.

Intracerebral haemorrhage accounts for 10 to 15 percent, usually the result of rupture of a small intracerebral degenerative microaneurysm.

The kidney The long-term renal damage produced by glomerular hypertension probably accountd for progressive glomerulosclerosis in essential hypertension.

Atheromatous renal vascular disease much more commonly causes renal impairment in elderly hypertensive subjects than younger patients with treated mild to moderate hypertension.

Malignant hypertension: Fibrinoid necrosis of damaged arteriole of kidney

Retinopathy Keith-Wagener classification Stage I: constriction of retinal arterioles only. Stage II: constriction and sclerosis of retinal arterioles. Stage III: hemorrhages and exudates in addition to vascular changes. Stages IV: papilledema.

Symptoms

Headache the classic hypertensive headache is present on walking in the morning, situated in the occipital region of the head, radiating to the frontal area, throbbing in quality, and wears off during the course of the day.

Most headaches in hypertensive patients are tension headaches not directly related to blood pressure. Nevertheless, effective treatment of hypertension reduces the incidence of headache.

Epistaxis Whilst epistaxis is not associated with mild hypertension, it is much more common in moderate to severe hypertension.

Nocturia this is one of the most frequent clinically apparent consequences of blood pressure elevation resulting from reduction in urineconcentrating capacity.

Others dizziness; flushed face; fatigue; palpitation.

Symptoms associated with target organ damage

Cardiovascular system Effort dyspnoea and orthopnoea suggest cardiac failure. Increased left ventricular mass is associated with decreased compliance and impaired cardiac output response to exercise.

Central nervous system Extensive disease of the perforating arteries may give rise to a lacunar state characterized by progressive pseudobulbar plasy and dementia.

Renal system Haematuria suggest the malignant phase of hypertension in the absence of any other cause.

Retinopathy Scotomas suggest fundal haemorrhages or exudates, whilst blurring of vision is associated with papilloedema.

Complications
Hypertensive emergencies Hypertensive encephalopathy Cerebrovascular disease Heart failure Chronic kidney disease Dissection of aorta

physical examination
SBP>=140 mmHg or DBP>=90 mmHg. Loud aortic second sound Other physical signs indicate target organ damage

Diagnosis

Diagnosis of primary hypertension depends on repeatedly demonstrating higher than-normal systolic and /or diastolic BP and excluding secondary hypertension.

Category

Systolic blood pressure (mmHg)

Diastolic blood pressure

Optimal blood pressure Normal blood pressure High-normal blood pressure Grade 1 Hypertension (mild) Grade 2 Hypertension (moderate) Grade 3 Hypertension (severe) Isolated Systolic Hypertension (Grade 1) Isolated Systolic Hypertension (Grade 2)

<120 <130 130-139 140-159 160-179 >180 140-159 >160

<80 (mmHg) <85 85-89 90-99 100-109 >110 <90 <90

CVD Risk Factors

Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus* Microalbuminuria or estimated GFR <60 ml/min Age (older than 55 for men, 65 for women)

Family history of premature CVD (men under age 55 or women under age 65)
*Components of the metabolic syndrome.

Cardiovascular risk category of hypertension

Blood pressuremmHg

Grade 1(SBP 140159 or DBP 9099) No other risk factors 12 risk factors
3 or more risk factors or diabetes or target organ damage

Grade 2(SBP 160179 or DBP 100109) Medium-risk

Grade 3(SBP 180 or DBP 110) High-risk

Low-risk Moderaterisk

Medium-risk

Very High-risk

High-risk

High-risk

Very High-risk

complications

Very Highrisk

Very High-risk

Very High-risk

Laboratory examinations

Serum potassium, creatine, blood glucose, blood lipids, complete blood count, uric acid, ECG, cardiac and chest x-ray exam and funduscopic exam for retinopathy. ABPM Double peaks and one hollow

Goals of Therapy
Reduce CVD and renal morbidity and mortality.

Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease. Achieve SBP goal especially in persons >50 years of age.

 Meta-analysis

of 61 prospective, observational studies 1 million adults 12.7 million person-years 7% reduction in

2 mmHg decrease in mean SBP

Blood Pressure Reduction of 2 mmHg Decreases the Risk of Cardiovascular Events by 710%

risk of ischaemic heart disease mortality 10% reduction in risk of stroke mortality

Lewington et al. Lancet 2002;360:190313

Lifestyle Modification

Weight reduction: the trial of hypertension prevention produced an average weight loss of 3.8 kg at 18 months, reduction of SBP and DBP by 2.9 and 2.3 mm Hg.

Exercise: Following increased physical activity, BP falls up 6-7 mm Hg for both SBP and DBP.

Sodium restriction Alcohol reduction and smoking cessation Stress reduction/relaxing training Dietary changes: low salt intake; potassium, magnesium and calcium supplementation; others.

Algorithm for Treatment of Hypertension

Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling Indications

With Compelling Indications

Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.

Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

Drug treatment
Diuretics -Blockers Calcium channel blockers ACE inhibitors Angiotensin II receptor blockers -Adrenergic blockers

Diuretics Indications : cardiac failure elderly patients systolic hypertension in elderly

 Blockers Indications :angina after myocardial infarction tachyarrhythmias cardiac failure (with care) Contraindications :asthma and chronic obstructive airway disease peripheral vascular disease

Calcium antagonists: Indications :systolic hypertension in the elderly Contraindications:heart block (verapamil and diltiazem)

ACEI Indications: cardiac failure left ventricular dysfunction after myocardiac infarction (higherrisk patients) diabetic nephropathy and other proteinuric renal disease Contraindications: pregnancy renovascular disease sodium and fluid depletion hyperkalaemia

ARB Indications: as for ACEI in presence of ACEI induced cough or intolerance Contraindications: as for ACEI

-Adrenergic blockers Indications: prostatism Contraindications: urinary incontience

Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs
Class of drug Alphablockers Compelling indications Benign prostatic hypertrophy Chronic renal disease, Type II diabetic nephropathy, proteinuric renal disease LV dysfunction post MI, intolerance of other antihypertensive drugs, proteinuric renal disease, chronic renal disease, heart failure Possible indications Compelling contraindications Urinary incontinence Pregnancy, renovascular disease

Caution Postural hypotension, heart failure Renal impairment PVD

ACEHeart failure, inhibitors LV dysfunction, post MI or established CVD, Type I diabetic nephropathy, 2o stroke prevention ARBs ACE inhibitorintolerance, Type II diabetic nephropathy, hypertension with LVH, heart failure in ACEintolerant patients, post MI

Renal impairment PVD

Pregnancy, renovascular disease

Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs
Class of drug Beta-blockers Compelling indications MI, Angina Possible indications Heart failure Caution Heart failure, PVD, Diabetes (except with CHD) Combination with betablockade Compelling contraindications Asthma/COPD, Heart block

CCBs (dihydropyridine) CCBs (rate limiting)

Elderly, ISH Angina

Angina Elderly

Heart block Heart failure Gout

Thiazide/thiazide- Elderly like diuretics ISH Heart failure 2 o stroke prevention

Classification and Management of BP for adults

Lifestyle BP SBP* DBP* modificati classification mmHg mmHg on Initial drug therapy Without compelling indication No antihypertensive drug indicated. With compelling indications Drug(s) for compelling indications.

Normal
Prehypertension

<120

and <80

Encourage
Yes

120139 or 8089

Stage 1 Hypertension
Stage 2 Hypertension

140159 or 9099

Yes

>160

or >100

Yes

Thiazide-type diuretics for most. Drug(s) for the May consider ACEI, ARB, BB, compelling indications. CCB, or combination. Other antihypertensive Two-drug combination for most drugs (diuretics, ACEI, (usually thiazide-type diuretic ARB, BB, CCB) as and ACEI or ARB or BB or needed. CCB).

*Treatment determined by highest BP category. Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

Other medications for hypertensive patients

Primary prevention
(1) Aspirin: use 75mg daily if patient is aged 50 years with blood pressure controlled to <150/90 mm Hg and either; target organ damage, diabetes mellitus, or 10 year risk of cardiovascular disease of 20% (measured by using the new Joint British Societies cardiovascular disease risk chart) (2) Statin: use sufficient doses to reach targets if patient is aged up to at least 80 years, with a 10 year risk of cardiovascular disease of 20% (measured by using the new Joint British Societies cardiovascular disease risk chart) and with total cholesterol concentration 3.5mmol/l (3) Vitaminsno benefit shown, do not prescribe

Other medications for hypertensive patients

Secondary prevention (including patients with type 2 diabetes)

(1) Aspirin: use for all patients unless contraindicated (2) Statin: use sufficient doses to reach targets if patient is aged up to at least 80 years with a total cholesterol concentration 3.5 mmol/l (3) Vitamins no benefit shown, do not prescribe

Lipid targets

Targets for lipid lowering Ideal TC<4.0mmol/l or LDL <2.0mmol/l or 25% in TC or 30% in LDL-C whichever is the greater TC <5.0mmol/l or LDL <3.0mmol/l or 25% in TC or 30% in LDL-C whichever is the greater

Audit

Some key points of the 2007 ESH and ESC guidelines

CVD Risk Factors

There are some new risk factors : fasting blood glucose 5.66.9mmol/L ; pulse pressure (in the elderly)

Target organ damage

ECG shows Left ventricular hypertrophy; PWV>12 m/s ; ABI<0.9; GFR<50ml/min1.75m2 creatinine clearance rate <60ml/min

Goals of treatment
-BP < 140/90 mmHg in all hypertensive patients < 130/80 mmHg in hypertensive patients with diabetes or renal disease

-Control of all cardiovascular risk factors

ESH - ESC Guidelines, J Hypertens 2008

About drug treatment

Diuretics, Blockers, Calcium channel blockers, ACE inhibitors and Angiotensin II receptor blockers can be used in onset and maintenane therapy. Diuretics combined with Blockers is not suitable for metabolic syndrome or high-risk diabetes patients. Low-dose combination therapy as first line treatment of mild-to-moderate hypertension

Screening and treatment of secondary forms of hypertension

1.

2.
3. 4. 5. 6. 7. 8.

Renal parenchymal disease Renovascular hypertension Phaeochromocytoma Primary aldosteronism Cushingsyndrome Obstructive sleep apnoea Coarctation of aorta Drug-induced hypertension